TY - JOUR
T1 - Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn cells
AU - Anamizu, Yorito
AU - Kawaguchi, Hiroshi
AU - Seichi, Atsushi
AU - Yamaguchi, Shinji
AU - Kawakami, Emiko
AU - Kanda, Naotoshi
AU - Matsubara, Shiro
AU - Kuro-o, Makoto
AU - Nabeshima, Yoichi
AU - Nakamura, Kozo
AU - Oyanagi, Kiyomitsu
N1 - Funding Information:
Acknowledgements The authors are indebted to Dr. K. Watabe of the Department of Molecular Neuropathology, and Dr. J. Kimura-Kuroda and Dr. I. Nagata (Department of Brain Structure, Tokyo Metropolitan Institute for Neuroscience), Dr. K. Honma (Graduate School of Pharmaceutical Science, University of Tokyo), Ms. M. Shinohara (Department of Anatomy, School of Veterinary Medicine, Tokyo University of Agriculture and Technology), and Dr. A. Mabuchi (Department of Orthopedic Surgery, Graduate School of Medicine, University of Tokyo) for their help during the research. This work was supported in part by grants from the Japanese Ministry of Health, Labor and Welfare (to Y.N., and Research on Psychiatric and Neurological Diseases and Mental Health (H16-kokoro-017 to K.O.)); the Japanese Ministry of Education, Science, Sports and Culture (nos. 12137201 to H.K., 12307031 to K.N., 14657376 to E.K. and 14580735 to K.O.) and the Japan Space Forum (to H.K.).
PY - 2005/5
Y1 - 2005/5
N2 - The klotho gene was identified in 1997 as the gene whose severe insufficiency (kl/kl) causes a syndrome resembling human aging, such as osteoporosis, arteriosclerosis, gonadal atrophy, emphysema, and short life span in a mouse strain. Regarding the gait disturbance reported in kl/kl mice, the present study examined the spinal cord of kl/kl mice, and revealed decreases in the number of large anterior horn cells (AHCs), the amount of cytoplasmic RNA, the number of ribosomes and rough endoplasmic reticulum (rER), and the activity of ribosomal (r) RNA gene transcription without significant loss of the total number of neurons in the ventral gray matter. Increased immunostaining of phosphorylated neurofilament in the AHCs and of glial fibrillary acidic protein in reactive astrocytes in the anterior horn of kl/kl mice were also observed. On the other hand, the posterior horn was quite well preserved. The results suggest that the kl/kl insufficiency causes atrophy and dysfunction of the spinal AHCs through decreased activity of rRNA gene transcription, which may reduce the amount of cytoplasmic RNA and the number of ribosomes and rER. These findings resemble those found in the spinal cord of patients with classic amyotrophic lateral sclerosis (ALS). The results show that klotho gene insufficiency causes dysfunction of the protein synthesizing system in the AHCs, and might indicate the klotho gene is involved in the pathological mechanism of classic ALS. The kl/kl is a new animal model of AHC degeneration, and may provide clues to understanding the etiology of classic ALS.
AB - The klotho gene was identified in 1997 as the gene whose severe insufficiency (kl/kl) causes a syndrome resembling human aging, such as osteoporosis, arteriosclerosis, gonadal atrophy, emphysema, and short life span in a mouse strain. Regarding the gait disturbance reported in kl/kl mice, the present study examined the spinal cord of kl/kl mice, and revealed decreases in the number of large anterior horn cells (AHCs), the amount of cytoplasmic RNA, the number of ribosomes and rough endoplasmic reticulum (rER), and the activity of ribosomal (r) RNA gene transcription without significant loss of the total number of neurons in the ventral gray matter. Increased immunostaining of phosphorylated neurofilament in the AHCs and of glial fibrillary acidic protein in reactive astrocytes in the anterior horn of kl/kl mice were also observed. On the other hand, the posterior horn was quite well preserved. The results suggest that the kl/kl insufficiency causes atrophy and dysfunction of the spinal AHCs through decreased activity of rRNA gene transcription, which may reduce the amount of cytoplasmic RNA and the number of ribosomes and rER. These findings resemble those found in the spinal cord of patients with classic amyotrophic lateral sclerosis (ALS). The results show that klotho gene insufficiency causes dysfunction of the protein synthesizing system in the AHCs, and might indicate the klotho gene is involved in the pathological mechanism of classic ALS. The kl/kl is a new animal model of AHC degeneration, and may provide clues to understanding the etiology of classic ALS.
KW - Anterior horn cell
KW - Cytoplasmic RNA
KW - Klotho
KW - Ribosomal RNA gene
KW - Transcription activity
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U2 - 10.1007/s00401-004-0971-7
DO - 10.1007/s00401-004-0971-7
M3 - Article
C2 - 15834732
AN - SCOPUS:21344432144
SN - 0001-6322
VL - 109
SP - 457
EP - 466
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 5
ER -